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TLR ‐Stimulated Eosinophils Mediate Recruitment and Activation of NK Cells In Vivo
Author(s) -
O'Flaherty S. M.,
Sutummaporn K.,
Häggtoft W. L.,
Worrall A. P.,
Rizzo M.,
Braniste V.,
Höglund P.,
Kadri N.,
Chambers B. J.
Publication year - 2017
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/sji.12554
Subject(s) - cxcl10 , chemokine , innate immune system , interleukin 21 , interleukin 12 , biology , immune system , immunology , microbiology and biotechnology , cytotoxic t cell , t cell , in vitro , biochemistry
Eosinophils like many myeloid innate immune cells can provide cytokines and chemokines for the activation of other immune cells upon TLR stimulation. When TLR ‐stimulated eosinophils were inoculated i.p. into wild‐type mice, and NK cells were rapidly recruited and exhibited antitumour cytotoxicity. However, when mice depleted of CD 11c + cells were used, a marked decrease in the number of recruited NK cells was observed. We postulated that CpG or LPS from the injected eosinophils could be transferred to host cells, which in turn could recruit NK cells. However, by inoculating mice deficient in TLR 4 or TLR 9 with LPS or CpG‐stimulated eosinophils respectively, NK cell recruitment was still observed alongside cytotoxicity and IFN γ production. CpG stimulation of eosinophils produced the pro‐inflammatory cytokine IL ‐12 and the chemokine CXCL 10, which are important for NK cell activation and recruitment in vivo . To demonstrate the importance of CXCL 10 in NK cell recruitment, we found that CpG‐stimulated eosinophils pretreated with the gut microbial metabolite butyrate had reduced expression and production of CXCL 10 and IL ‐12 and concomitantly were poor at recruitment of NK cells and inducing IFN γ in NK cells. Therefore, eosinophils like other innate immune cells of myeloid origin can conceivably stimulate NK cell activity. In addition, products of the gut microbiota can be potential inhibitors of NK cell.